A Phase I Study of Subcutaneous "CYT 107" (Interleukin-7) in Refractory Metastatic Melanoma or Renal Cell Carcinoma
- Determine the safety of recombinant interleukin-7 (IL-7) in patients with metastatic
melanoma or locally advanced or metastatic renal cell carcinoma.
- Confirm the previously documented safety profile of non-glycosylated IL-7 in these
- Determine the safety of higher doses of recombinant IL-7 in these patients.
- Determine the maximum tolerated dose of recombinant IL-7 in these patients.
- Determine the biologically active dose of recombinant IL-7 in these patients.
- Determine the pharmacokinetics and pharmacodynamics of recombinant IL-7 in these
- Compare the biological and clinical effects of recombinant IL-7 with non-glycosylated
IL-7 in these patients.
- Determine the potential antitumor effect of recombinant IL-7 in these patients.
- Determine the dose and administration schedule of recombinant IL-7 in these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to lymphocyte
count (normal lymphocyte count [CD4+ T cells > 400/mm^3] vs lymphopenic [CD4+ T cells <
400/mm^3]). Patients are assigned to 1 of 2 treatment groups.
- Group 1 (normal lymphocyte count): Patients receive recombinant interleukin-7 (IL-7)
subcutaneously once a week (to determine an active dose) for up to 3 weeks in the
absence of disease progression or unacceptable toxicity.
- Group 2 (lymphopenic): Patients receive recombinant IL-7 subcutaneously once a week for
up to 3 weeks at one dose level below the active dose determined in group 1.
Cohorts of 3-6 patients from each group receive escalating doses of recombinant IL-7 until
the maximum tolerated dose (MTD) is determined. The MTD is the defined as the dose preceding
that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 30
additional patients may be treated at the MTD.
Patients undergo blood and bone marrow collection periodically for pharmacokinetic,
pharmacodynamic, and immunological studies. Samples are analyzed for the presence of
antibodies and proteins via ELISA; CD3, CD4, and CD8 T cell counts, CD127, Ki-67, and Bcl-2
expression in CD4+ and CD8+ T cells, and CD19 B cell counts via flow cytometry; and clonal B
cell proliferation via PCR and flow cytometry.
After completion of study treatment, patients are followed at 3 months.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of recombinant interleukin-7 (IL-7)
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|